Cesium carbonate → isopropyl ((S)-7-cyano-4-(((2R,3S)-3-hydroxytetrahydrofuran-2-yl)Methyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-2-yl)carbaMate

HRID 1928581ノート

反応式

HRID 1928581 の反応式
[CH:1]([O:4][C:5](=[O:21])[NH:6][C@@H:7]1[CH2:20][C:10]2[NH:11][C:12]3[CH:13]=[CH:14][C:15]([C:18]#[N:19])=[CH:16][C:17]=3[C:9]=2[CH2:8]1)([CH3:3])[CH3:2].CC1C=CC(S(O[CH2:33][C@@H:34]2[C@@H:38]([OH:39])[CH2:37][CH2:36][O:35]2)(=O)=O)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN1CCCC1.C(OCC)(=O)C>[CH:1]([O:4][C:5](=[O:21])[NH:6][C@@H:7]1[CH2:20][C:10]2[N:11]([CH2:33][C@@H:34]3[C@@H:38]([OH:39])[CH2:37][CH2:36][O:35]3)[C:12]3[CH:13]=[CH:14][C:15]([C:18]#[N:19])=[CH:16][C:17]=3[C:9]=2[CH2:8]1)([CH3:3])[CH3:2]

参加物

6

反応物 3

HCID 10796Cesium carbonateHCID 58271236[(2R,3S)-3-hydroxytetrahydrofuran-2-yl]methyl 4-methylbenzenesulfonateHCID 66933207(S)-(7-Cyano-1,2,3,4-tetrahydrocyclopenta[b]indol-2-yl)carbamic Acid Isopropyl Ester

生成物 1

HCID 52914985isopropyl ((S)-7-cyano-4-(((2R,3S)-3-hydroxytetrahydrofuran-2-yl)Methyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-2-yl)carbaMate収率 72.7%

試薬・触媒・溶媒 2

HCID 84541-Methylpyrrolidine溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
65 °C

実験手順

A mixture of ((S)-7-cyano-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl)-carbamic acid isopropyl ester (2.50 g, 8.82 mmol), [(2R,3S)-3-hydroxytetrahydrofuran-2-yl]methyl 4-methylbenzenesulfonate (3.10 g, 11.38 mmol), and cesium carbonate (5.00 g, 15.35 mmol) in N-methylpyrrolidine (25 mL) is heated in a 65° C. oil bath overnight. After cooling to ambient temperature, the reaction is diluted with ethyl acetate (120 mL) and washed with water (3×100 mL) and brine. The organic portion is dried over sodium sulfate, filtered, and concentrated to dryness. The resulting residue is purified by medium pressure liquid chromatography, eluting with ethyl acetate. Fractions containing pure product are combined and concentrated to afford 2.46 g (72%) of the title compound. LC-ES/MS m/z 384.2 [M+H]+, TR=1.90 min. (Symyx Draw 3.1 (IUPAC Name) provides the following name for the compound of Example 1: Isopropyl N-[(2S)-7-cyano-4-[[(2R,3S)-3-hydroxytetrahydrofuran-2-yl]methyl]-2,3-dihydro-1H-cyclopenta[b]indol-2-yl]carbamate.)

後処理

  1. temperatureAfter cooling to ambient temperature
  2. washwashed with water (3×100 mL) and brine
  3. dry with materialThe organic portion is dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. customThe resulting residue is purified by medium pressure liquid chromatography
  7. washeluting with ethyl acetate
  8. additionFractions containing pure product
  9. concentrationconcentrated

出典と根拠

ORDレコード
ord-23a0aff16c6547539192ddf4e67fd943
出典データセット
uspto-grants-2012_05
特許番号
US08183388B2

反応ノート

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